Plant isoprene emissions are known to contribute to abiotic stress tolerance, especially during episodes of high temperature and drought, and during cellular oxidative stress. Recent studies have shown that genetic transformations to add or remove isoprene emissions cause a cascade of cellular modifications that include known signaling pathways, and interact to remodel adaptive growth-defense tradeoffs. The most compelling evidence for isoprene signaling is found in the shikimate and phenylpropanoid pathways, which produce salicylic acid, alkaloids, tannins, anthocyanins, flavonols and other flavonoids; all of which have roles in stress tolerance and plant defense. Isoprene also influences key gene expression patterns in the terpenoid biosynthetic pathways, and the jasmonic acid, gibberellic acid and cytokinin signaling networks that have important roles in controlling inducible defense responses and influencing plant growth and development, particularly following defoliation. In this synthesis paper, using past studies of transgenic poplar, tobacco and Arabidopsis, we present the evidence for isoprene acting as a metabolite that coordinates aspects of cellular signaling, resulting in enhanced chemical defense during periods of climate stress, while minimizing costs to growth. This perspective represents a major shift in our thinking away from direct effects of isoprene, for example, by changing membrane properties or quenching ROS, to indirect effects, through changes in gene expression and protein abundances. Recognition of isoprene's role in the growth-defense tradeoff provides new perspectives on evolution of the trait, its contribution to plant adaptation and resilience, and the ecological niches in which it is most effective.